A Novel Function for Hog1 MAP kinase in Control of White-Opaque Switching and Its Stability in Candida albicans

Candida albicans is the opportunistic human fungal pathogen found in the gastrointestinal and urogenital tracts of healthy people. However, for the people who are immumocompromised, C. albicans can cause invasive candidiasis, which would result in systemic infection and high mortality rate. A phenotypic transition between White and Opaque states in C. albicans is associated with its virulence in different colonizing niches. Furthermore, comparised with white cells, opaque cells could escape attacks from macrophages. Besides, Opaque cells, but not white cells, have been shown to have the exclusive ability of mating. The White-Opaque phenotypic transition is majorly controlled by the Wor1 transcriptional feedback loop. Some environmental clues, including PH, oxidative stress, carbon sources, and temperature, also have influence on regulating the White-Opaque switching. Hog1 MAP kinase has been recognized as the main regulator for adapting to environmental oxidative stress of C. albicans. Therefore, we hypothesized that Hog1 MAP kinase not only has the ability to adapt to environmental stresses, but also has the ability to regulate the White-Opaque switching. In this study, knocking out the HOG1 gene in a/a and α/α cells resulted in 100% opaque cell formation on SC medium at both 25℃ and 37℃ + 5% CO2 culture condition (mimic gastrointestinal condition). However, hog1/wor1 mutants remained in the white state, suggesting that Wor1 still plays an important role in opaque cell formation. To indentify the potential downstram transcritption factors regulated by Hog1, deletion of both MSN2 and MSN4 did not induce the White-to-Opaque switching. The opaque cells forming from hog1 mutants are less stable than those of the wild-type, only 80% of the colonies remained in opaque phenotype, whereas the stability of opaque cells in the wild-type and complementary strain is near 95%. Besides, only 15% of the hog1 mutant cells formed pheromone-induced mating projection, whereas the shmoo formation of the wild-type reached to 48%. The average length of mating projections generated from hog1 mutants is 10.54 μm, which is shorter than those of the wild-type (24.39 μm). As the expectation, the mating efficiency of hog1 mutants significantly decreased to 2.71% compared to the wild-type (9.92%) and complementary strain (8.15%). In summary, my studies revealed that the Hog1 MAP kinase of C. albicans not only is required for oxidative stress, but also is involved in White-Opaque switching and the characteristics of opaque cells.